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Coluracetam (MKC-231) is a racetam drug purported to be a cognitive enhancing drug. It is able to preserve choline uptake into neurons when they are otherwise impaired, but currently there is no evidence for inherent nootropic effects.

Our evidence-based analysis on coluracetam features 14 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Research Breakdown on Coluracetam

1Sources and Structure


Coluracetam (full structural name of 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro2,3-b quinolin-4-yl)acetoamide and codenames of MKC-231 or BCI-540) is a racetam compound formulated as a nootropic for the purpose of cognitive enhancement.

Coluracetam is a synthetic drug of the racetam family designed to support cholinergic function, particular for the treatment of Alzheimer's


A known metabolite is hydroxylated coluracetam on the 2-carbon of the pyrrolidinone backbone, it is sometimes referred to as M-MKC-231.[1] It appears inactive on the main mechanism of action coluracetam is known for (increasing HACU).[1]

Coluracetam is a highly modified pyrrolidinone backbone



Plasma concentrations of coluracetam in rats following oral ingestion of 10mg/kg have been noted to be 4.289+/-0.641µg/mL (30 minutes), 0.717+/-0.350µg/mL (3 hours), and 0.037+/-0.010µg/mL (24 hours).[2] The kinetics following seven or fourteen days of supplementation was similar.[2]

Coluracetam has been detected in plasma following oral ingestion, and appears to be able to reach high levels within 30 minutes and is already on the decline within 3 hours


Oral intake of 10mg/kg coluracetam to rats has been noted to be detected in the brain at 30 minutes post-ingestion (210+/-54ng/g wet weight) and is detectable at three hours (30+/-16ng/g wet weight) but not a day after ingestion.[2] Supplementation of coluracetam for 7-14 days does not alter these kinetics.[2]

Coluracetam can be detected in neural tissue within 30 minutes of ingestion, and is significantly reduced in concentration within 3 hours


3.1Cholinergic Neurotransmission

High affinity choline uptake (HACU) is the uptake of choline at the synpase for the purpose of acetylcholine synthesis, and is seen as a rate-limiting step of acetylcholine synthesis. Coluracetam appears to associated with these transporters.[1]

Velocity of HACU correlates well with cholinergic neuron activity[3][4] and HACU is usually perturbed in Alzheimer's disease[5][6] (some contradictory data[7]).

HACU appears to be a rate-limiting step of acetylcholine synthesis

Coluracetam has been noted to, in rats treated with choline uptake inhibitors (such as AF64A[8]), increase choline uptake and acetylcholine synthesis[9] associated with an increase in Vmax (1.7-fold) and Bmax (1.6-fold) at 10nM concentration.[1] KM appears unaffected from coluracetam,[1] but is not inherently impaired by the research toxin AF64A.

HACU does not appear to be influence in hippocampal slices derived from rats not treated with choline uptake inhibitors,[10] with both the KM and Vmax being unaffected as well.[1] Additionally, ligand (HC-3) binding to cholinergic receptors in normal rats appears unaffected.[1]

Coluracetam appears to be able to increase the activity of this step when it is otherwise impaired but preliminary evidence suggests that this is not an inherent effect

Hippocampal concentrations of acetylcholine that are reduced by HACU inhibitors are able to be partially preserved with oral treatment of 300-1,000mcg/kg coluracetam over twelve days with no acute effect nor benefit with 3mg/kg.[11]

Coluracetam may be able to attenuate learning deficits seen with choline uptake inhibitors as assessed by water maze, and is active orally at the dosage of 1-10mg/kg in rats.[10] Elsewhere, the effects of 300-3,000mcg coluracetam have not been detected after single administration but were present (near full restoration of performance in a T-maze) after 12 days.[11] Benefits to cognition in this research model (AF64A treated) have been noted at 1-3mg/kg coluracetam to extend for up to two days after supplement cessation despite no detectable coluracetam in the brain (no significant benefit on the third day).[2]

One study has noted that the cholinergic dysfunction induced in rats by phencyclidine (a research drug to induce symptoms associated with schizophrenia[12]) also given 3mg/kg coluracetam twice daily resulted in significantly less cognitive disturbance (assessed by object recognition) although it was without effect on passive avoidance learning nor locomotor changes.[13]

Coluracetam appears to preserve and/or normalize cholinergic dysfunction in the presence of underactive of chemically impaired HACU, but there is no research to support an inherent cognitive boosting effect

3.2Glutaminergic Neurotransmission

In cultured corticol neurons, coluracetam is able to reduce the excitotoxicity caused by either glutamate or calcium influx but is ineffective against nitric oxide donors.[14] Practical significance of this data is uncertain as the tests were conducted at 10µM, a higher than normal concentration for this molecule.[14]

Suggests protective effects, but this information may not be relevant due to the high concentration used


  1. ^ a b c d e f g Takashina K, et al. MKC-231, a choline uptake enhancer: (3) Mode of action of MKC-231 in the enhancement of high-affinity choline uptake. J Neural Transm. (2008)
  2. ^ a b c d e Bessho T, et al. MKC-231, a choline-uptake enhancer: (1) long-lasting cognitive improvement after repeated administration in AF64A-treated rats. J Neural Transm. (2008)
  3. ^ Simon JR, Atweh S, Kuhar MJ. Sodium-dependent high affinity choline uptake: a regulatory step in the synthesis of acetylcholine. J Neurochem. (1976)
  4. ^ Yamamura HI, Snyder SH. High affinity transport of choline into synaptosomes of rat brain. J Neurochem. (1973)
  5. ^ Rodríguez-Puertas R, et al. Selective cortical decrease of high-affinity choline uptake carrier in Alzheimer's disease: an autoradiographic study using 3H-hemicholinium-3. J Neural Transm Park Dis Dement Sect. (1994)
  6. ^ Rylett RJ, Ball MJ, Colhoun EH. Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer's disease. Brain Res. (1983)
  7. ^ Slotkin TA, et al. Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: implications for etiology and therapy. Proc Natl Acad Sci U S A. (1990)
  8. ^ Fisher A, et al. Long-term central cholinergic hypofunction induced in mice by ethylcholine aziridinium ion (AF64A) in vivo. J Pharmacol Exp Ther. (1982)
  9. ^ Takashina K, et al. MKC-231, a choline uptake enhancer: (2) Effect on synthesis and release of acetylcholine in AF64A-treated rats. J Neural Transm. (2008)
  10. ^ a b Bessho T, et al. Effect of the novel high affinity choline uptake enhancer 2-(2-oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro{2,3-b} quinolin-4-yl)acetoamide on deficits of water maze learning in rats. Arzneimittelforschung. (1996)
  11. ^ a b Murai S, et al. MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice. J Neural Transm Gen Sect. (1994)
  12. ^ Morris BJ, Cochran SM, Pratt JA. PCP: from pharmacology to modelling schizophrenia. Curr Opin Pharmacol. (2005)
  13. ^ Shirayama Y, et al. Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats. Eur Neuropsychopharmacol. (2007)
  14. ^ a b Akaike A, et al. Protective effect of MKC-231, a novel high affinity choline uptake enhancer, on glutamate cytotoxicity in cultured cortical neurons. Jpn J Pharmacol. (1998)